Ex vivo T-cell–depleted allogeneic stem cell transplantation for hematologic malignancies: The search for an optimum transplant T-cell dose and T-cell add-back strategy

Abstract

BackgroundT-cell depletion (TCD) of allogeneic stem cell transplants (SCT) can reduce graft-versus-host disease but may negatively affect transplant outcome by delaying immune recovery. To optimize TCD in HLA-matched siblings with hematologic malignancies, we explored varying the transplant CD3+ T-cell dose between 2 and 50 × 104/kg (corresponding to 3–4 log depletion) and studied the impact of 0–6 × 107/kg CD3+ donor lymphocyte infusion (DLI) “add-back” on immune recovery post-SCT. MethodsTwo hundred seventeen consecutive patients (age range, 10–75 years) with hematologic malignancy (excluding chronic leukemias) underwent ex vivo TCD SCT from HLA-identical sibling donors from 1994–2015. Ninety-four patients had standard-risk disease (first remission acute leukemia [AL] and early stage myelodysplastic syndromes [MDS]) and 123 had high-risk disease (AL beyond first complete remission, advanced MDS or refractory B-cell malignancy). ResultsMedian follow-up was 8.5 years. At 20 years post-SCT, overall survival (OS) was 40%, nonrelapse mortality (NRM) was 27% and relapse incidence was 39%. Factors affecting outcome in multivariate analysis were transplantation era, with OS increasing from 38% in the period 1994–2000 to 58% in 2011–2015, disease risk (hazard ratio [HR], 1.68 for high risk) and increasing age (HR, 1.19 per decade). Neither the T-cell dose or the add back of T cells in the first 100 days had any effect on OS, NRM and relapse. ConclusionsOutcomes for TCD SCT have greatly improved. However, our data do not support the need to precisely manipulate transplant CD3+ T-cell dose provided at least 3-log depletion is achieved or the use of T-cell add-back. Future improvements for TCD SCT await better strategies to prevent relapse, especially in high-risk recipients.